Research Highlights
Protein post-translational modification – tyrosine dephosphorylation promotes autophagy precursor fusion and autophagosome formation

The formation of the autophagosome is a dynamic and tightly regulated process. SNARE-mediated membrane fusion plays a pivotal role in various stages of autophagic process including the autophagosome biogenesis and autophagosome-lysosome fusion. However, the molecular regulation of SNAREs in autophagy remains largely unclear. ATG16L1 precursor homotypic fusion contributes to development of phagophore structures and is critical for the biogenesis of autophagosomes. In this study, we discovered a novel role of the protein tyrosine phosphatase PTPN9 in the regulation of ATG16L1 vesicle fusion and early autophagosome formation. PTPN9 interacted with and dephosphorylated tyrosine-phosphorylated the Q-SNARE protein VTI1B, promoting SNARE complex assembly, ATG16L1 homotypic fusion, and autophagic flux. Our findings reveal a new role of SNARE dephosphorylation in the regulation of autophagosome precursor maturation and autophagosome biogenesis. We further showed that Drosophila Ptpmeg2 ameliorated polyglutamine (polyQ)-induced toxicity in retina, suggesting that PTPN9/Ptpmeg2 could potentially be targeted therapeutically to modulate autophagy activity in diseases with autophagic dysfunction.

Article title: “PTPN9-mediated dephosphorylation of VTI1B promotes ATG16L1 precursor fusion and autophagosome formation”

Article link: https://doi.org/10.1080/15548627.2020.1838117

Authors: He-Yen Chou, Yi-Tang Lee, Yuchieh Jay Lin, Jung-Kun Wen, Wen-Hsin Peng, Pei-Lien Hsieh, Shu-Yu Lin, Chin-Chun Hung, Guang-Chao Chen*

Updated: 2020.11.18